High-throughput Identification of Genotype-specific Cancer Vulnerabilities in Mixtures of Barcoded Tumor Cell Lines

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2016 Mar 2

PMID 26928769

Citations 172

Authors

Channing Yu

Aristotle M Mannan

Griselda Metta Yvone

Kenneth N Ross

Yan-Ling Zhang

Melissa A Marton

Bradley R Taylor

Andrew Crenshaw

Joshua Z Gould

Pablo Tamayo

Barbara A Weir

Aviad Tsherniak

Bang Wong

Levi A Garraway

Alykhan F Shamji

Michelle A Palmer

Michael A Foley

Wendy Winckler

Stuart L Schreiber

Andrew L Kung

Todd R Golub

Affiliations

Soon will be listed here.

Abstract

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo.

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